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The characteristics and clinical significance of atypical mitosis in breast cancer

Lashen, Ayat; Toss, Michael S.; Alsaleem, Mansour; Green, Andrew R.; Mongan, Nigel P.; Rakha, Emad

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Authors

Ayat Lashen

Michael S. Toss

Mansour Alsaleem

NIGEL MONGAN nigel.mongan@nottingham.ac.uk
Professor of Oncology

EMAD RAKHA Emad.Rakha@nottingham.ac.uk
Professor of Breast Cancer Pathology



Abstract

Atypical mitosis is considered a feature of malignancy, however, its significance in breast cancer (BC) remains elusive. Here, we aimed to assess the clinical value of atypical mitoses in BC and to explore their underlying molecular features. Atypical and typical mitotic figures were quantified and correlated with clinicopathological variables in a large cohort of primary BC tissue sections (n = 846) using digitalized hematoxylin and eosin whole-slide images (WSIs). In addition, atypical mitoses were assessed in The Cancer Genome Atlas (TCGA) BC dataset (n = 1032) and were linked to the genetic alterations and pathways. In this study, the median of typical mitoses was 17 per 3 mm2 (range 0–120 mitoses), while the median of atypical mitoses was 4 (range 0–103 mitoses). High atypical mitoses were significantly associated with parameters characteristic of aggressive tumor behavior. The total number of mitoses, and a high atypical-to-typical mitoses ratio (>0.27) were associated with poor BC specific survival (BCSS), (p = 0.04 and 0.01, respectively). The atypical-to-typical mitoses ratio dichotomized triple negative-BC (TNBC) patients into two distinct groups in terms of the association with the outcome, while the overall number of mitoses was not. Moreover, TNBC patients with high atypical-to-typical mitoses ratio treated with adjuvant chemotherapy were associated with shorter survival (p = 0.003). Transcriptomic analysis of the TCGA-BRCA cohort dichotomized based on atypical mitoses identified 2494 differentially expressed genes. These included genes linked to pathways involved in chromosomal localization and segregation, centrosome assembly, spindle and microtubule formation, regulation of cell cycle and DNA repair. To conclude, the atypical-to-typical mitoses ratio has prognostic value independent of the overall mitotic count in BC patients and could predict the response to chemotherapy in TNBC.

Citation

Lashen, A., Toss, M. S., Alsaleem, M., Green, A. R., Mongan, N. P., & Rakha, E. (2022). The characteristics and clinical significance of atypical mitosis in breast cancer. Modern Pathology, 35, 1341-1348. https://doi.org/10.1038/s41379-022-01080-0

Journal Article Type Article
Acceptance Date Mar 27, 2022
Online Publication Date May 2, 2022
Publication Date 2022-10
Deposit Date Apr 5, 2022
Publicly Available Date Mar 29, 2024
Journal Modern Pathology
Print ISSN 0893-3952
Electronic ISSN 1530-0285
Publisher Springer Science and Business Media LLC
Peer Reviewed Peer Reviewed
Volume 35
Pages 1341-1348
DOI https://doi.org/10.1038/s41379-022-01080-0
Keywords Pathology and Forensic Medicine
Public URL https://nottingham-repository.worktribe.com/output/7708315
Publisher URL https://www.nature.com/articles/s41379-022-01080-0

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